14-36516817-CAAAA-CAAAAA

Variant names:

• chr14-36516817-C-CA
• rs5807883
• NM_001079668.3:c.*460dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001079668.3(NKX2-1):​c.*460dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.42 (12453 hom., cov: 0)
  • Exomes 𝑓: 0.35 (73 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -1.44
• Publications: 1 publications found

Genes affected

NKX2-1 (HGNC:11825): (NK2 homeobox 1) This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]

SFTA3 (HGNC:):

SFTA3 (HGNC:18387): (surfactant associated 3) Involved in wound healing. Located in cytoplasm and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079668.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-1	NM_001079668.3	MANE Select	c.*460dupT		3_prime_UTR	Exon 3 of 3	NP_001073136.1	P43699-3
	NKX2-1	NM_003317.4		c.*460dupT		3_prime_UTR	Exon 2 of 2	NP_003308.1	P43699-1
	SFTA3	NR_161364.1		n.89+2650dupT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-1	ENST00000354822.7	TSL:1 MANE Select	c.*460dupT		3_prime_UTR	Exon 3 of 3	ENSP00000346879.6	P43699-3
	NKX2-1	ENST00000498187.6	TSL:1	c.*460dupT		3_prime_UTR	Exon 2 of 2	ENSP00000429607.2	P43699-1
	SFTA3	ENST00000546983.2	TSL:4	n.373+2167dupT		intron	N/A	ENSP00000449302.2	F8VVG2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 59489 AN: 142150 Hom.: 12457 Cov.: 0

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.346 AC: 25368 AN: 73350 Hom.: 73 Cov.: 0 AF XY: 0.347 AC XY: 11701 AN XY: 33746

African (AFR) AF: 0.287 AC: 1006 AN: 3510

American (AMR) AF: 0.292 AC: 645 AN: 2210

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1637 AN: 4656

East Asian (EAS) AF: 0.395 AC: 4009 AN: 10158

South Asian (SAS) AF: 0.305 AC: 208 AN: 682

European-Finnish (FIN) AF: 0.314 AC: 27 AN: 86

Middle Eastern (MID) AF: 0.328 AC: 149 AN: 454

European-Non Finnish (NFE) AF: 0.343 AC: 15590 AN: 45460

Other (OTH) AF: 0.342 AC: 2097 AN: 6134

GnomAD4 genome AF: 0.418 AC: 59483 AN: 142206 Hom.: 12453 Cov.: 0 AF XY: 0.418 AC XY: 28728 AN XY: 68768

African (AFR) AF: 0.325 AC: 12251 AN: 37680

American (AMR) AF: 0.383 AC: 5552 AN: 14478

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1532 AN: 3342

East Asian (EAS) AF: 0.603 AC: 2962 AN: 4916

South Asian (SAS) AF: 0.420 AC: 1848 AN: 4400

European-Finnish (FIN) AF: 0.431 AC: 3786 AN: 8792

Middle Eastern (MID) AF: 0.404 AC: 109 AN: 270

European-Non Finnish (NFE) AF: 0.461 AC: 30196 AN: 65462

Other (OTH) AF: 0.413 AC: 822 AN: 1988

Alfa AF: 0.272 Hom.: 504

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Benign hereditary chorea (1)
-	1	-	Brain-lung-thyroid syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5807883; hg19: chr14-36986022; COSMIC: COSV61388040; COSMIC: COSV61388040;